This is a project for the study, by single-crystal x-ray methods, of the interactions and recognition mechanisms between macromolecules. The main projects of interest are: 1. Crystallography of prokaryotic and eukaryotic cytochromes c and cytochrome oxidase, including cocrystallization of Pseudomonas cytochrome oxidase (cd) with its electron donors azurin or cytochrome c551. 2. The structure analysis of the lactose repressor/operator complex. 3. Crystallography of small DNA molecules (4 to 12 base pairs) and their complexes with intercalating agents and other drugs. Small crystals of cytochrome cd suitable for x-ray analysis have been obtained, and cocrystallization trials are in progress. The lac repressor-operator crystals are still too small for x-ray analysis, but experiments are continuing. The structure of the double-helical DNA molecule deoxy (HO-CpGpCpG-OH) or CGCG has been solved, and found to be a left-handed helix with alternating syn-anti sugar-base conformation. Covalent heavy atom derivatives of CCGG are being prepared, and analysis is under way. Structure analyses of the dodecamer CGCGAATTCGCG and the entire lac operator are planned.